Ca2+ flux through promiscuous cardiac Na+ channels: slip-mode conductance.
The tetrodotoxin-sensitive sodium ion (Na+) channel is opened by cellular depolarization and favors the passage of Na+ over other ions. Activation of the beta-adrenergic receptor or protein kinase A in rat heart cells transformed this Na+ channel into one that is promiscuous with respect to ion selectivity, permitting calcium ions (Ca2+) to permeate as readily as Na+. Similarly, nanomolar concentrations of cardiotonic steroids such as ouabain and digoxin switched the ion selectivity of the Na+ channel to this state of promiscuous permeability called slip-mode conductance. Slip-mode conductance of the Na+ channel can contribute significantly to local and global cardiac Ca2+ signaling and may be a general signaling mechanism in excitable cells.
Santana
L F
LF
Department of Molecular Biology, Medical Biotechnology Center and School of Medicine, University of Maryland, 725 West Lombard Street, Baltimore, MD 21201, USA.
Gómez
A M
AM
Lederer
W J
WJ
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004077:Digoxin / Q000494:pharmacology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; D019837:Ryanodine Receptor Calcium Release Channel; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin; D010042:Ouabain; D004077:Digoxin; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D002118:Calcium